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Port-Site and Wound Recurrences in Cancer Surgery: Incidence - Pathogenesis - Prevention PDF

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M.A. Reymond· H.J. Bonjer· F. K6ckerling (Eds.) Port-Site and Wound Recurrences in Cancer Surgery Springer-V erlag Berlin Heidelberg GmbH M.A. Reymond· H.J. Bonjer· F. Kockerling (Eds.) Port-Site and Wound Recurrences in Cancer Surgery lncidence - Pathogenesis - Prevention Foreword by Sir Alfred Cuschieri With 60 Figures and 20 Tables Springer Marc A. Reymond, M.D., Associate Professor of Surgery, Department of Surgery, University Hospital of Magdeburg, Leipziger Strasse 44 39120 Magdeburg, Germany H. Jaap Bonjer, M.D., Ph.D., Head ofLaparoscopic Surgery and Acting Head of Endocrine Surgery, University Hospital Rotterdam Dijkzigt Hospital, PO Box 2040, 3000 CA, Rotterdam, The Netherlands Ferdinand Kockerling, M.D., Professor of Surgery and Head Department of Surgery and Center for Minimally Invasive Surgery, Hanover Hospital, Roesebeckstrasse 15 Silo ah, 30449 Hannover, Germany ISBN 978-3-642-63117-7 Cataloging-in-Publication Data applied for Die Deutsche Bibliothek - CIP-Einheitsaufnahme Reymond, Marc A.: Port site and wound recurrences in cancer surgery : incidence - pathogenesis - prevention / Marc A. Reymond ; H. J. Bonjer ; F. Kockerling. Foreword by Alfred Cuschieri. Transl. from the German by A. Jack. - Berlin; Heidelberg ; New York; Barcelona ; Hong Kong ; London ; Mailand ; Paris; Singapur ; Tokio : Springer, 2000 ISBN 978-3-642-63117-7 ISBN 978-3-642-57028-5 (eBook) DOI 10.1007/978-3-642-57028-5 This work is subject to copyright. AH rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illus- trations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current vers ion, and permission for use must always be obtained from Springer-Verlag. Viola- tions are liable for prosecution under the German Copyright Law. © Springer-Veriag Berlin Heidelberg 2000 Originally published by Springer-Verlag Berlin Heidelberg in 2000 Softcover reprint of the hardcover 18t edition 2000 The use of general descriptive names, registered names, trademarks, etc. in this publica- tion does not imply, even in the absence of a specific statement, that such names are ex- empt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about the application of operative techniques and medications contained in this book. In every individual case the user must check such information by consult ing the relevant literature. Cover design: design & production GmbH, D-69121 Heidelberg Typesetting: FotoSatz Pfeifer GmbH, D-82166 Grăfelfing SPIN: 10755673 24/3135 - 5 4 3 2 1 o Foreword During the past 9 years, reports of 'port-site' deposits following laparoscopic surgery for malignancy, especially laparoscopic resection of colonic cancer, have cast a shadow on the wisdom of the laparoscopic approach in the surgical man- agement in patients with cancer. Those reports of port-site deposits, some 90 cases reported in the literature up to 1999, have opened a 'can of worms' and highlighted the scarcity of our knowledge on cancer cell migration from solid tu- mors and the factors that underlie their successful implantation in surgical wounds both in the presence and absence of a positive pressure pneumoperito- neum. The jury is out even in relation to the effect of the healing surgical access wound - do the biochemical and cellular repair processes and the associated growth factors enhance or prevent implantation of exfoliated viable tumor cells? Whatever the answer to this question, it is clear that tumor cells do implant in healing surgical wounds and the key question is whether this is facilitated by lap- aroscopic surgery with CO2 pneumoperitoneum compared to the traditional surgical exposure. It is known that tumors shed malignant cells into the blood stream, the peritoneal cavity and in the case of hollow organs, intraluminally. Equally there is good evidence that surgical and instrumental manipulation of tumors induce exfoliation of viable tumor cells. The entire subject has been be-devilled by imponderable questions such as 'What is the nature of port- site/wound deposits in strict pathological terms? What it the gold standard technique for detection and quantitation of exfoliated tumor cells? What are the appropriate tumor models and animals for experimen- tal investigation of this important problem, and how does the inevitable non- specific immune depression caused by surgery impact on the optimal surgical approach for resection of operable cancer?' The controversy on port-site/wound deposits has also demonstrated, as never before, that it is easy to formulate a hy- pothesis on presumed mechanisms of cancer cell migration and implantation but much more difficult to prove what actually happens even with meticulous and planned animal experimentation. Furthermore, in taking a clinical problem such as port-site deposits to the laboratory, the appropriateness of the model used is crucial to the valid extrapolation of the experimental results to the clini- cal situation. It is not surprising, therefore, that practicing surgeons have been confused by the vast reported literature, at times seemingly contradictory, on clinical and ex- perimental work on port-site tumor deposits since the early reports of such oc- currences. A detailed reappraisal of the subject of port-site and wound deposits in all their aspects based on the published clinical and experimental work was necessary and long overdue. This is precisely what the editors of this monograph 'Port-Site and Wound Recurrence in Cancer' have done with considerable suc- cess. The account is comprehensive, written by authors who have been involved in research in the field and covers both the experimental work and the "clinical VI Foreword aspects of port -site/wound deposits. The monograph evaluates critically what is known and equally what is conjectural at this stage of our knowledge on the sub- ject. From a research standpoint, the limitations of the various tumor models used and the useful conclusions that can be drawn are clearly and objectively outlined in this book. There is much information and sound advice in this book for both researchers and clinical surgeons. In the final analysis 'port-site and wound deposits' have to be considered as local recurrence and as with other instances of treatment failure, the surgeon factor is important if not paramount. Rather than being a specific complication oflaparoscopic surgery, port-site deposits have in part to be regarded as the af- termath of poor surgical technique that is at least as much to blame as some poorly understood biological mechanism. This to me is an important message that is repeatedly stressed in this seminal monograph. Its success as a reference manual on the subject is assured as the editors and their contributors have ad- dressed this important subject in an objective fashion based on evidence and not conjecture. Prof Sir Alfred Cuschieri Preface Application of laparoscopic surgery to cancer has been associated with an in- creased number of secondary tumors implanted into the abdominal wall, termed "port-site recurrences". This complication reported for hundreds of patients in the literature could discourage many surgeons to apply minimally invasive sur- gery to cancer. However, in the meantime, the pathogenesis of port-site recur- rences has been systematically addressed in basic and clinical research, and a number of efficient preventive strategies have been developed. The large number of published studies makes it difficult for the laparoscopic surgeon, the general surgeon, the gastroenterologists, and the interested oncologist to get a synthetic and critical overview over this novel field. In this book we have united chapters from most of the groups which are active worldwide in experimental and clinical research on port-site recurrences. The problem of wound recurrence in open cancer surgery is also discussed in detail. This should allow the reader to get an organized insight into the different patho- genic mechanisms of port-site recurrences, notably as to where the cells from which the secondary tumor arises come from, how they are dispersed, and how local effects in the port-site wound can favor implantation. Moreover, the book contains well illustrated guidelines to show preventive measures applicable by any surgeon. These can reduce substantially the incidence of port-site recur- rence, allowing a safer application of minimally invasive surgery in cancer. Contents 1 Definition of Port-Site and Wound Recurrences in Cancer Surgery A. Tannapfel, C. Wittekind Introduction ................................................... . Biological Basis of Port -Site Recurrences ........................... . Location and Diagnosis of Port -Site Recurrences. . . . . . . . . . . . . . . . . . . .. 2 Time of Presentation of Port -Site Recurrences ....................... 3 Summary ...................................................... 4 References ..................................................... 4 2 A Case Report 1. Inan, M.A. Reymond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 6 3 Abdominal Wall Recurrences in Open Surgery L. Stocchi, H. Nelson Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8 Abdominal Wall Recurrence in Colorectal Cancer .................... 8 Autopsy Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8 Second-Look Laparotomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 9 Data from Prospective Adjuvant Therapy Trials . . . . . . . . . . . . . . . . . . . . .. 9 Abdominal Wall Recurrence After Malignancies Other than Colorectal Cancer...... ....... ... .... ... .... ... ... .. .... .... ........ ... 9 Summary ...................................................... 11 References ..................................................... 11 4 Port-Site Recurrences in Laparoscopic Surgery Ph. Wittich, H.I. Bonjer Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 12 Gynecological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 12 Colorectal Cancer ............................................... 13 Gallbladder Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 16 Urological Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 17 Diagnostic Laparoscopy .......................................... 17 References ..................................................... 18 5 Port-Site Recurrences in Thoracoscopic Surgery R. Downey, M.A. Reymond Dissemination After Fine Needle Puncture .......................... 21 Chest Wall Recurrence After Thoracotomy . . . . . . . . . . . . . . . . . . . . . . . . .. 22 Port-Site Recurrences After VATS .................................. 22 Preventive Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 23 References ..................................................... 24 X Contents 6 Port Site Recurrences in Colon and Rectal Cancers: Randomized Studies T. Sonoda, J.w. Milsom Prospective Data ............ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 26 Randomized Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 26 Influence of the Surgeon on the Incidence of Port -Site Recurrences .... 27 References .................................................... 27 7 Pathogenesis: Tumor Cell Lines and Application in Experimental Animal Studies J.w. Fleshman Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29 Tumor Xenografts/Tissue Type ................................... 29 Tumor Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29 Mouse ...................................................... 29 Rat ......................................................... 31 Human ..................................................... 32 Experimental Protocols ......................................... 33 Documentation of Port -Site Recurrence Relationship to Laparoscopy 34 Investigation of the Mechanism of Cell Movement to and Establishment of Tumor at Port -Sites . . . . . . . . . . . . . . . . . . . . . . . . .. 36 Factors Influencing Tumor Growth and Trocar Site Implantation .... 39 Prevention of Tumor Implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 41 Conclusions ................................................... 42 References .................................................... 42 8 Pathogenesis: Transportation of Tumor Cells in Animal Studies M.L. Texler, P.J. Hewett Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 44 Research to Date ............................................... 44 Small Animal Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 44 Large Animal Models ................... . . . . . . . . . . . . . . . . . . . . .. 44 Discussion .................................................... 48 Radiolabelled Cell Models in the Pig ............................ 49 Segmental Colonic Resection Studies. . . . . . . . . . . . . . . . . . . . . . . . . . .. 50 Conclusions ................................................... 50 References .................................................... 51 9 Pathogenesis: Local Effects in the Wound in Animal Studies C.A. Jacobi, H.J. Bonjer Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 52 Experimental Tumor Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 52 Chimney Effect and Aerosolization of Tumor Cells ................ 52 Influence of Different Gases and Elevated Intraperitoneal Pressure. .. 54 Local Wound Conditions, Ischemia and Local Necrosis ............ 54 Local Effects on Mesothelial Cells and Peritoneal Structure ... . . . . .. 55 Changes ofIntra- and Extracellular pH and Calcium Levels in Peritoneal Macrophages or Tumor Cells ........................ 55 Effects on Peritoneal Macrophages and Cytokine Production. . . . . . .. 56 Conclusions ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 57 References .................................................... 57 10 Pathogenesis: Immunological Aspects of Animal Studies S. W. Lee, R.L. Whelan Introduction ................................................... 60 Immune Suppression Following Open Surgery ...................... 60 Contents XI Immune Function After Laparoscopic Procedures . . . . . . . . . . . . . . . . . .. 61 DTH Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 61 Lymphocyte Proliferation Assays ............................... 62 Lymphocyte Subpopulation Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 63 Monocyte Function and Antigen Expression ..................... 63 Neutrophil Function .......................................... 64 Natural Killer Cell Activity ..................................... 64 Mechanism of Postoperative Immunosuppression . . . . . . . . . . . . . . . . . .. 65 Relationship Between Postoperative Immunosuppression and Tumor Growth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 65 Immune Function and Port-site Tumors ........................... 66 Local Versus Systemic Immune Function ........................... 66 Conclusions ................................................... 67 References .................................................... 67 11 Pathogenesis: Free Viable Cancer Cells and Cancer Cell Liberation in Clinical Studies P. Buchmann, D. Christen, 1. Stocchi, H. Nelson Introduction ................................................... 69 Predictive Value of Exfoliated Cells ................................ 69 Correlation with Local Recurrence and Survival. . . . . . . . . . . . . . . . . . . .. 71 References .................................................... 72 12 Pathogenesis: Transportation of Tumor Cells in Clinical Studies M. Pross, K. Ridwelski, M.A. Reymond Introduction ................................................... 74 Mechanisms Involved in the Transport of Tumor Cells ............... 74 Data from the Literature ......................................... 78 References .................................................... 79 13 Pathogenesis: Immunological Aspects of Clinical Studies D. Mutter, M. Aprahamian Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 81 The Acute Phase Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 81 Interleukin-6 ................................................ 82 C-Reactive Protein ........................................... 83 The Other Cytokines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 84 Interleukin -1~ ............................................... 84 Tumor Necrosis Factor-u ...................................... 84 Other Cytokines ............................................. 85 The Immune Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 85 Total White Blood Cell Changes ................................ 85 Leukocyte Subpopulation Changes .............................. 86 Changes in Immune Cell Functions ............................. 87 Other Host Defense Mechanisms ................................. 88 Histamine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 88 Production of Reactive Oxygen Species ... . . . . . . . . . . . . . . . . . . . . . .. 88 Nitric Oxide, Inducible NO Synthase and Peroxynitrite . . . . . . . . . . . .. 88 Conclusion .................................................... 89 References .................................................... 89 14 Mechanical Means For Prevention of Trocar Site Cancer Implantation M.E. Franklin Jr., J.A. Diaz-E, J. Balli Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 91 Experimental Data ............................................. 91

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